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Gene | ALK |
Variant | F1174V |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | ALK F1174V lies within the protein kinase domain of the Alk protein (UniProt.org). F1174V results in constitutive activation of the Alk protein in cell culture (PMID: 21242967) and has been demonstrated to occur as a secondary resistance mutation in the context of ALK fusions (PMID: 24675041), and therefore, is predicted to lead to a gain of Alk protein function. |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK act mut ALK F1174V ALK mutant ALK F1174X ALK F1174V |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220831A>C |
cDNA | c.3520T>G |
Protein | p.F1174V |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29220831A>C | c.3520T>G | p.F1174V | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29220831A>C | c.3520T>G | p.F1174V | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220831A>C | c.3520T>G | p.F1174V | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | predicted - resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | lung non-small cell carcinoma | predicted - sensitive | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK initially responded to Xalkori (crizotinib), but then progressed due to acquisition of the secondary resistance mutation, ALK F1174V, and then responded to treatment with Alecensa (alectinib), demonstrating a complete response in one lung nodule and a 44% decrease in size in a second lung nodule (PMID: 26464158). | 26464158 |
EML4 - ALK ALK F1174V | lung non-small cell carcinoma | resistant | Crizotinib | Clinical Study | Actionable | In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079). | 24736079 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Gilteritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | resistant | Entrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). | 33627640 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Iruplinalkib | Preclinical - Cell culture | Actionable | In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578). | 35421578 |
EML4 - ALK ALK F1174V | Advanced Solid Tumor | sensitive | Ensartinib | Preclinical - Cell culture | Actionable | In a preclinical study, Ensacove (ensartinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK F1174V | lung adenocarcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a complete response with a progression-free survival of 12.3 months, overall survival of 28.1 months, and a duration of treatment of 13.8 months in a patient with lung adenocarcinoma harboring EML4-ALK (e2:e20) with ALK F1174V (PMID: 39500140). | 39500140 |
EML4 - ALK ALK I1171S ALK F1174V | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). | 26464158 |
EML4 - ALK ALK F1174V ALK G1202R | lung non-small cell carcinoma | sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041). | 24675041 |
EML4 - ALK ALK C1156Y ALK F1174V | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
EML4 - ALK ALK F1174V ALK L1196M | Advanced Solid Tumor | resistant | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). | 29650534 |
ALK F1174V ALK amp | neuroblastoma | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). | 29907598 |
ALK F1174V ALK amp | neuroblastoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited proliferation of neuroblastoma cells harboring ALK amplification and ALK F1174V in culture (PMID: 29907598). | 29907598 |
ALK F1174V ALK amp | neuroblastoma | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) inhibited downstream signaling and proliferation, and induced apoptosis in a neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 31852910). | 31852910 |
ALK F1174V ALK pos | lung non-small cell carcinoma | predicted - sensitive | Ensartinib | Case Reports/Case Series | Actionable | In a Phase II clinical trial, Ensacove (ensartinib) treatment resulted in an objective response in 71% (5/7, all partial responses) of patients with ALK-positive non-small cell lung cancer harboring ALK F1174L (n=5) or ALK F1174V (n=1) (PMID: 31628085; NCT0321569). | 31628085 |
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A | lung adenocarcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A were identified in the post-progression biopsy of a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e13:e20), who previously responded to Xalkori (crizotinib) treatment (PMID: 36093526). | 36093526 |
EML4 - ALK ALK E1129V ALK I1171T ALK F1174C ALK F1174L ALK F1174V ALK G1269A | lung adenocarcinoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 10 months in a patient with lung adenocarcinoma harboring EML4-ALK (e13:e20), ALK E1129V, F1174C, F1174L, F1174V, I1171T, and G1269A (PMID: 36093526). | 36093526 |
ALK rearrange ALK F1174V | lung non-small cell carcinoma | predicted - resistant | Alectinib | Case Reports/Case Series | Actionable | In a clinical study, ALK F1174V was identified in a patient with non-small cell lung cancer harboring an ALK rearrangement after progression on second-line Alecensa (alectinib) treatment following Xalkori (crizotinib) resistance (Ann of Oncol (2022) 33 (suppl_7): S448-S554). | detail... |
EML4 - ALK ALK I1171T ALK F1174V | lung non-small cell carcinoma | predicted - sensitive | Ceritinib | Case Reports/Case Series | Actionable | In a Phase I trial, Zykadia (ceritinib) treatment resulted in a partial response in a patient with non-small cell lung cancer harboring EML4-ALK (e13:e20), ALK F1174V, and ALK I1171T (PMID: 34890832; NCT01283516). | 34890832 |
ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Idasanutlin + TAE684 | Preclinical - Cell culture | Actionable | In a preclinical study, TAE684 and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |
ALK F1174V ALK amp TP53 wild-type | neuroblastoma | sensitive | Alectinib + Idasanutlin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth and induced apoptosis in a TP53 wild-type neuroblastoma cell line harboring ALK F1174V and ALK amplification in culture (PMID: 36602782). | 36602782 |